The role of the serotonin 2B receptor (5-HT2BR) in enamel formation and mineralization was explored in adult 5HT2BR knockout (KO) mice compared with wild-type (WT) mice. In the molar, quantitative data obtained by micro-computed tomography imaging showed that the overall volume of the enamel layer was firmly reduced in KO mice. Defective mineralization was ascertained by energy-dispersive X-ray microanalysis. We also observed, using scanning electron microscopy, that parazones in the KO mice included two or three helicoidally twisted rods within Hunter–Schreger bands, instead of a single rod, as found in the WT mice. Minor disturbances were also detected in the incisors of KO mice. Structural modifications, thinner enamel crystallites, and porosities observed in KO mice indicate that the 5-HT2BR-mediated signaling pathways as part of the enamel formation process. These data provide a basis for evaluating the role of 5-HT2BR in ameloblast functions. Defects observed in the mineralization and structure of enamel in KO mice highlight that the 5-HT2BR interferes with the mechanisms directing amelogenesis.

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